NZ525380A - Non-fucosylated forms of Cripto and their use as tumor blocking agents - Google Patents
Non-fucosylated forms of Cripto and their use as tumor blocking agentsInfo
- Publication number
- NZ525380A NZ525380A NZ525380A NZ52538001A NZ525380A NZ 525380 A NZ525380 A NZ 525380A NZ 525380 A NZ525380 A NZ 525380A NZ 52538001 A NZ52538001 A NZ 52538001A NZ 525380 A NZ525380 A NZ 525380A
- Authority
- NZ
- New Zealand
- Prior art keywords
- seq
- cripto
- polypeptide
- amino acid
- cancer
- Prior art date
Links
- 206010028980 Neoplasm Diseases 0.000 title claims abstract description 28
- 101100369076 Mus musculus Tdgf1 gene Proteins 0.000 title description 69
- 239000002981 blocking agent Substances 0.000 title 1
- 101000835745 Homo sapiens Teratocarcinoma-derived growth factor 1 Proteins 0.000 claims abstract description 187
- 102100026404 Teratocarcinoma-derived growth factor 1 Human genes 0.000 claims abstract description 126
- 125000003275 alpha amino acid group Chemical group 0.000 claims abstract description 40
- 238000006467 substitution reaction Methods 0.000 claims abstract description 24
- 108090000765 processed proteins & peptides Proteins 0.000 claims description 90
- 102000004196 processed proteins & peptides Human genes 0.000 claims description 76
- 229920001184 polypeptide Polymers 0.000 claims description 70
- 101000835739 Homo sapiens Putative teratocarcinoma-derived growth factor 3 Proteins 0.000 claims description 63
- 102100026407 Putative teratocarcinoma-derived growth factor 3 Human genes 0.000 claims description 63
- 235000001014 amino acid Nutrition 0.000 claims description 46
- 150000001413 amino acids Chemical class 0.000 claims description 29
- 230000000694 effects Effects 0.000 claims description 26
- 230000033581 fucosylation Effects 0.000 claims description 21
- 239000008194 pharmaceutical composition Substances 0.000 claims description 21
- 230000004048 modification Effects 0.000 claims description 20
- 238000012986 modification Methods 0.000 claims description 20
- 108020004707 nucleic acids Proteins 0.000 claims description 18
- 102000039446 nucleic acids Human genes 0.000 claims description 18
- 150000007523 nucleic acids Chemical class 0.000 claims description 18
- 238000000034 method Methods 0.000 claims description 17
- 210000004881 tumor cell Anatomy 0.000 claims description 17
- 108091035707 Consensus sequence Proteins 0.000 claims description 15
- 125000000539 amino acid group Chemical group 0.000 claims description 15
- FWMNVWWHGCHHJJ-SKKKGAJSSA-N 4-amino-1-[(2r)-6-amino-2-[[(2r)-2-[[(2r)-2-[[(2r)-2-amino-3-phenylpropanoyl]amino]-3-phenylpropanoyl]amino]-4-methylpentanoyl]amino]hexanoyl]piperidine-4-carboxylic acid Chemical compound C([C@H](C(=O)N[C@H](CC(C)C)C(=O)N[C@H](CCCCN)C(=O)N1CCC(N)(CC1)C(O)=O)NC(=O)[C@H](N)CC=1C=CC=CC=1)C1=CC=CC=C1 FWMNVWWHGCHHJJ-SKKKGAJSSA-N 0.000 claims description 14
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 claims description 13
- 230000004663 cell proliferation Effects 0.000 claims description 13
- 201000011510 cancer Diseases 0.000 claims description 12
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 12
- 108010076504 Protein Sorting Signals Proteins 0.000 claims description 11
- 201000010099 disease Diseases 0.000 claims description 11
- 230000012010 growth Effects 0.000 claims description 11
- 230000002401 inhibitory effect Effects 0.000 claims description 10
- 230000035755 proliferation Effects 0.000 claims description 9
- 235000004279 alanine Nutrition 0.000 claims description 8
- 238000002360 preparation method Methods 0.000 claims description 8
- 230000011664 signaling Effects 0.000 claims description 8
- 208000026310 Breast neoplasm Diseases 0.000 claims description 7
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 claims description 7
- 206010006187 Breast cancer Diseases 0.000 claims description 6
- 206010009944 Colon cancer Diseases 0.000 claims description 6
- 239000004471 Glycine Substances 0.000 claims description 6
- 238000000338 in vitro Methods 0.000 claims description 6
- 229920001059 synthetic polymer Polymers 0.000 claims description 6
- 208000001333 Colorectal Neoplasms Diseases 0.000 claims description 5
- 230000000295 complement effect Effects 0.000 claims description 5
- 206010005003 Bladder cancer Diseases 0.000 claims description 3
- 230000004568 DNA-binding Effects 0.000 claims description 3
- 208000008839 Kidney Neoplasms Diseases 0.000 claims description 3
- 208000035561 Leukaemic infiltration brain Diseases 0.000 claims description 3
- 206010058467 Lung neoplasm malignant Diseases 0.000 claims description 3
- 206010033128 Ovarian cancer Diseases 0.000 claims description 3
- 206010061535 Ovarian neoplasm Diseases 0.000 claims description 3
- 206010038389 Renal cancer Diseases 0.000 claims description 3
- 208000007097 Urinary Bladder Neoplasms Diseases 0.000 claims description 3
- 208000002495 Uterine Neoplasms Diseases 0.000 claims description 3
- 201000007455 central nervous system cancer Diseases 0.000 claims description 3
- 201000010039 central nervous system leukemia Diseases 0.000 claims description 3
- HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 claims description 3
- 201000010982 kidney cancer Diseases 0.000 claims description 3
- 201000005202 lung cancer Diseases 0.000 claims description 3
- 208000020816 lung neoplasm Diseases 0.000 claims description 3
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 3
- 208000013755 primary melanoma of the central nervous system Diseases 0.000 claims description 3
- 201000005112 urinary bladder cancer Diseases 0.000 claims description 3
- 206010046766 uterine cancer Diseases 0.000 claims description 3
- 108010070675 Glutathione transferase Proteins 0.000 claims description 2
- 108060003951 Immunoglobulin Proteins 0.000 claims description 2
- 206010060862 Prostate cancer Diseases 0.000 claims description 2
- 208000000236 Prostatic Neoplasms Diseases 0.000 claims description 2
- 230000003213 activating effect Effects 0.000 claims description 2
- 102000018358 immunoglobulin Human genes 0.000 claims description 2
- 102000005720 Glutathione transferase Human genes 0.000 claims 1
- 230000000903 blocking effect Effects 0.000 abstract description 3
- 210000004027 cell Anatomy 0.000 description 35
- 239000012634 fragment Substances 0.000 description 32
- 229940024606 amino acid Drugs 0.000 description 28
- 108090000623 proteins and genes Proteins 0.000 description 28
- 235000018102 proteins Nutrition 0.000 description 21
- 102000004169 proteins and genes Human genes 0.000 description 21
- 230000027455 binding Effects 0.000 description 20
- 102100028701 General vesicular transport factor p115 Human genes 0.000 description 16
- 101000767151 Homo sapiens General vesicular transport factor p115 Proteins 0.000 description 16
- 239000000047 product Substances 0.000 description 16
- 108020004414 DNA Proteins 0.000 description 15
- AYFVYJQAPQTCCC-GBXIJSLDSA-N L-threonine Chemical compound C[C@@H](O)[C@H](N)C(O)=O AYFVYJQAPQTCCC-GBXIJSLDSA-N 0.000 description 15
- 239000005089 Luciferase Substances 0.000 description 14
- 239000002299 complementary DNA Substances 0.000 description 14
- ATDGTVJJHBUTRL-UHFFFAOYSA-N cyanogen bromide Chemical compound BrC#N ATDGTVJJHBUTRL-UHFFFAOYSA-N 0.000 description 14
- 238000011282 treatment Methods 0.000 description 14
- 102000055846 human TDGF1 Human genes 0.000 description 13
- 230000002829 reductive effect Effects 0.000 description 13
- 239000013598 vector Substances 0.000 description 13
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 12
- SHZGCJCMOBCMKK-DHVFOXMCSA-N L-fucopyranose Chemical compound C[C@@H]1OC(O)[C@@H](O)[C@H](O)[C@@H]1O SHZGCJCMOBCMKK-DHVFOXMCSA-N 0.000 description 12
- 238000004949 mass spectrometry Methods 0.000 description 12
- 239000000523 sample Substances 0.000 description 12
- 108010030544 Peptidyl-Lys metalloendopeptidase Proteins 0.000 description 11
- 239000005557 antagonist Substances 0.000 description 11
- 150000001875 compounds Chemical class 0.000 description 9
- 239000013612 plasmid Substances 0.000 description 9
- SHZGCJCMOBCMKK-UHFFFAOYSA-N D-mannomethylose Natural products CC1OC(O)C(O)C(O)C1O SHZGCJCMOBCMKK-UHFFFAOYSA-N 0.000 description 8
- PNNNRSAQSRJVSB-SLPGGIOYSA-N Fucose Natural products C[C@H](O)[C@@H](O)[C@H](O)[C@H](O)C=O PNNNRSAQSRJVSB-SLPGGIOYSA-N 0.000 description 8
- AYFVYJQAPQTCCC-UHFFFAOYSA-N Threonine Natural products CC(O)C(N)C(O)=O AYFVYJQAPQTCCC-UHFFFAOYSA-N 0.000 description 8
- 239000004473 Threonine Substances 0.000 description 8
- 102000004190 Enzymes Human genes 0.000 description 7
- 108090000790 Enzymes Proteins 0.000 description 7
- 108060001084 Luciferase Proteins 0.000 description 7
- 210000004978 chinese hamster ovary cell Anatomy 0.000 description 7
- VHJLVAABSRFDPM-QWWZWVQMSA-N dithiothreitol Chemical compound SC[C@@H](O)[C@H](O)CS VHJLVAABSRFDPM-QWWZWVQMSA-N 0.000 description 7
- 230000001105 regulatory effect Effects 0.000 description 7
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 6
- 108091034117 Oligonucleotide Proteins 0.000 description 6
- 238000004128 high performance liquid chromatography Methods 0.000 description 6
- 238000001727 in vivo Methods 0.000 description 6
- 238000012510 peptide mapping method Methods 0.000 description 6
- 239000002904 solvent Substances 0.000 description 6
- 241000894007 species Species 0.000 description 6
- 108020004705 Codon Proteins 0.000 description 5
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 5
- 230000008859 change Effects 0.000 description 5
- 238000006243 chemical reaction Methods 0.000 description 5
- 239000003636 conditioned culture medium Substances 0.000 description 5
- 238000002474 experimental method Methods 0.000 description 5
- 238000009396 hybridization Methods 0.000 description 5
- 239000002502 liposome Substances 0.000 description 5
- 238000000816 matrix-assisted laser desorption--ionisation Methods 0.000 description 5
- 230000035772 mutation Effects 0.000 description 5
- 102220225095 rs751226641 Human genes 0.000 description 5
- 150000003839 salts Chemical class 0.000 description 5
- 108010022366 Carcinoembryonic Antigen Proteins 0.000 description 4
- 102100025475 Carcinoembryonic antigen-related cell adhesion molecule 5 Human genes 0.000 description 4
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 4
- 241000699670 Mus sp. Species 0.000 description 4
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 4
- 238000004458 analytical method Methods 0.000 description 4
- 238000000137 annealing Methods 0.000 description 4
- 230000009286 beneficial effect Effects 0.000 description 4
- 230000001419 dependent effect Effects 0.000 description 4
- 230000014509 gene expression Effects 0.000 description 4
- 239000000243 solution Substances 0.000 description 4
- 238000012360 testing method Methods 0.000 description 4
- 238000001890 transfection Methods 0.000 description 4
- 238000003146 transient transfection Methods 0.000 description 4
- 102000005572 Cathepsin A Human genes 0.000 description 3
- 108010059081 Cathepsin A Proteins 0.000 description 3
- 241001559589 Cullen Species 0.000 description 3
- 239000006137 Luria-Bertani broth Substances 0.000 description 3
- 241001465754 Metazoa Species 0.000 description 3
- 241000699666 Mus <mouse, genus> Species 0.000 description 3
- 102000000447 Peptide-N4-(N-acetyl-beta-glucosaminyl) Asparagine Amidase Human genes 0.000 description 3
- 108010055817 Peptide-N4-(N-acetyl-beta-glucosaminyl) Asparagine Amidase Proteins 0.000 description 3
- 238000003776 cleavage reaction Methods 0.000 description 3
- 238000010367 cloning Methods 0.000 description 3
- 125000000151 cysteine group Chemical group N[C@@H](CS)C(=O)* 0.000 description 3
- 230000003247 decreasing effect Effects 0.000 description 3
- 238000002330 electrospray ionisation mass spectrometry Methods 0.000 description 3
- 238000005516 engineering process Methods 0.000 description 3
- 230000000670 limiting effect Effects 0.000 description 3
- 210000004962 mammalian cell Anatomy 0.000 description 3
- 238000005259 measurement Methods 0.000 description 3
- 238000002844 melting Methods 0.000 description 3
- 230000008018 melting Effects 0.000 description 3
- 231100000350 mutagenesis Toxicity 0.000 description 3
- 238000002703 mutagenesis Methods 0.000 description 3
- 231100000219 mutagenic Toxicity 0.000 description 3
- 230000003505 mutagenic effect Effects 0.000 description 3
- 239000002773 nucleotide Substances 0.000 description 3
- 125000003729 nucleotide group Chemical group 0.000 description 3
- 239000002953 phosphate buffered saline Substances 0.000 description 3
- 230000026731 phosphorylation Effects 0.000 description 3
- 238000006366 phosphorylation reaction Methods 0.000 description 3
- 238000000746 purification Methods 0.000 description 3
- 230000007017 scission Effects 0.000 description 3
- 238000012163 sequencing technique Methods 0.000 description 3
- 239000011780 sodium chloride Substances 0.000 description 3
- 239000006228 supernatant Substances 0.000 description 3
- 230000001225 therapeutic effect Effects 0.000 description 3
- 210000001519 tissue Anatomy 0.000 description 3
- 238000001262 western blot Methods 0.000 description 3
- MTCFGRXMJLQNBG-REOHCLBHSA-N (2S)-2-Amino-3-hydroxypropansäure Chemical compound OC[C@H](N)C(O)=O MTCFGRXMJLQNBG-REOHCLBHSA-N 0.000 description 2
- 244000105975 Antidesma platyphyllum Species 0.000 description 2
- 108091026890 Coding region Proteins 0.000 description 2
- 108020004635 Complementary DNA Proteins 0.000 description 2
- 238000001712 DNA sequencing Methods 0.000 description 2
- BWGNESOTFCXPMA-UHFFFAOYSA-N Dihydrogen disulfide Chemical compound SS BWGNESOTFCXPMA-UHFFFAOYSA-N 0.000 description 2
- 206010061818 Disease progression Diseases 0.000 description 2
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 2
- 102000003886 Glycoproteins Human genes 0.000 description 2
- 108090000288 Glycoproteins Proteins 0.000 description 2
- ZRALSGWEFCBTJO-UHFFFAOYSA-N Guanidine Chemical compound NC(N)=N ZRALSGWEFCBTJO-UHFFFAOYSA-N 0.000 description 2
- 241000282412 Homo Species 0.000 description 2
- 101000622304 Homo sapiens Vascular cell adhesion protein 1 Proteins 0.000 description 2
- DCXYFEDJOCDNAF-REOHCLBHSA-N L-asparagine Chemical compound OC(=O)[C@@H](N)CC(N)=O DCXYFEDJOCDNAF-REOHCLBHSA-N 0.000 description 2
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 2
- QJPWUUJVYOJNMH-VKHMYHEASA-N L-homoserine lactone Chemical group N[C@H]1CCOC1=O QJPWUUJVYOJNMH-VKHMYHEASA-N 0.000 description 2
- KZSNJWFQEVHDMF-BYPYZUCNSA-N L-valine Chemical compound CC(C)[C@H](N)C(O)=O KZSNJWFQEVHDMF-BYPYZUCNSA-N 0.000 description 2
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 2
- 239000004472 Lysine Substances 0.000 description 2
- TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 description 2
- 241000699660 Mus musculus Species 0.000 description 2
- 108091028043 Nucleic acid sequence Proteins 0.000 description 2
- 241000283973 Oryctolagus cuniculus Species 0.000 description 2
- 102100038551 Peptide-N(4)-(N-acetyl-beta-glucosaminyl)asparagine amidase Human genes 0.000 description 2
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 2
- 239000004698 Polyethylene Substances 0.000 description 2
- 239000002202 Polyethylene glycol Substances 0.000 description 2
- 102100033237 Pro-epidermal growth factor Human genes 0.000 description 2
- 108700008625 Reporter Genes Proteins 0.000 description 2
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 2
- 108091023040 Transcription factor Proteins 0.000 description 2
- 102000040945 Transcription factor Human genes 0.000 description 2
- KZSNJWFQEVHDMF-UHFFFAOYSA-N Valine Natural products CC(C)C(N)C(O)=O KZSNJWFQEVHDMF-UHFFFAOYSA-N 0.000 description 2
- 210000001015 abdomen Anatomy 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 239000000427 antigen Substances 0.000 description 2
- 108091007433 antigens Proteins 0.000 description 2
- 102000036639 antigens Human genes 0.000 description 2
- 239000002246 antineoplastic agent Substances 0.000 description 2
- 210000001367 artery Anatomy 0.000 description 2
- 235000003704 aspartic acid Nutrition 0.000 description 2
- OQFSQFPPLPISGP-UHFFFAOYSA-N beta-carboxyaspartic acid Natural products OC(=O)C(N)C(C(O)=O)C(O)=O OQFSQFPPLPISGP-UHFFFAOYSA-N 0.000 description 2
- 230000004071 biological effect Effects 0.000 description 2
- 230000037396 body weight Effects 0.000 description 2
- 210000000481 breast Anatomy 0.000 description 2
- 210000004899 c-terminal region Anatomy 0.000 description 2
- 239000004202 carbamide Substances 0.000 description 2
- 239000000969 carrier Substances 0.000 description 2
- 238000005119 centrifugation Methods 0.000 description 2
- 238000012512 characterization method Methods 0.000 description 2
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 2
- 210000001072 colon Anatomy 0.000 description 2
- 238000002591 computed tomography Methods 0.000 description 2
- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 2
- 230000005750 disease progression Effects 0.000 description 2
- 238000011156 evaluation Methods 0.000 description 2
- 239000013613 expression plasmid Substances 0.000 description 2
- 239000013604 expression vector Substances 0.000 description 2
- 230000006870 function Effects 0.000 description 2
- 238000010353 genetic engineering Methods 0.000 description 2
- 150000004676 glycans Chemical class 0.000 description 2
- 125000003630 glycyl group Chemical group [H]N([H])C([H])([H])C(*)=O 0.000 description 2
- 235000009424 haa Nutrition 0.000 description 2
- 238000001802 infusion Methods 0.000 description 2
- 238000011221 initial treatment Methods 0.000 description 2
- 238000002347 injection Methods 0.000 description 2
- 239000007924 injection Substances 0.000 description 2
- 238000004020 luminiscence type Methods 0.000 description 2
- 239000011159 matrix material Substances 0.000 description 2
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- 238000010369 molecular cloning Methods 0.000 description 2
- 238000011580 nude mouse model Methods 0.000 description 2
- 210000004197 pelvis Anatomy 0.000 description 2
- 108040002068 peptide-N4-(N-acetyl-beta-glucosaminyl)asparagine amidase activity proteins Proteins 0.000 description 2
- 229920001223 polyethylene glycol Polymers 0.000 description 2
- 108091033319 polynucleotide Proteins 0.000 description 2
- 102000040430 polynucleotide Human genes 0.000 description 2
- 239000002157 polynucleotide Substances 0.000 description 2
- 230000009467 reduction Effects 0.000 description 2
- 108091008146 restriction endonucleases Proteins 0.000 description 2
- 238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 2
- 239000001488 sodium phosphate Substances 0.000 description 2
- 229910000162 sodium phosphate Inorganic materials 0.000 description 2
- 238000007920 subcutaneous administration Methods 0.000 description 2
- 239000000758 substrate Substances 0.000 description 2
- RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 description 2
- 239000004474 valine Substances 0.000 description 2
- 238000005406 washing Methods 0.000 description 2
- 230000003442 weekly effect Effects 0.000 description 2
- 238000005303 weighing Methods 0.000 description 2
- NMWKYTGJWUAZPZ-WWHBDHEGSA-N (4S)-4-[[(4R,7S,10S,16S,19S,25S,28S,31R)-31-[[(2S)-2-[[(1R,6R,9S,12S,18S,21S,24S,27S,30S,33S,36S,39S,42R,47R,53S,56S,59S,62S,65S,68S,71S,76S,79S,85S)-47-[[(2S)-2-[[(2S)-4-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-amino-3-methylbutanoyl]amino]-3-methylbutanoyl]amino]-3-hydroxypropanoyl]amino]-3-(1H-imidazol-4-yl)propanoyl]amino]-3-phenylpropanoyl]amino]-4-oxobutanoyl]amino]-3-carboxypropanoyl]amino]-18-(4-aminobutyl)-27,68-bis(3-amino-3-oxopropyl)-36,71,76-tribenzyl-39-(3-carbamimidamidopropyl)-24-(2-carboxyethyl)-21,56-bis(carboxymethyl)-65,85-bis[(1R)-1-hydroxyethyl]-59-(hydroxymethyl)-62,79-bis(1H-imidazol-4-ylmethyl)-9-methyl-33-(2-methylpropyl)-8,11,17,20,23,26,29,32,35,38,41,48,54,57,60,63,66,69,72,74,77,80,83,86-tetracosaoxo-30-propan-2-yl-3,4,44,45-tetrathia-7,10,16,19,22,25,28,31,34,37,40,49,55,58,61,64,67,70,73,75,78,81,84,87-tetracosazatetracyclo[40.31.14.012,16.049,53]heptaoctacontane-6-carbonyl]amino]-3-methylbutanoyl]amino]-7-(3-carbamimidamidopropyl)-25-(hydroxymethyl)-19-[(4-hydroxyphenyl)methyl]-28-(1H-imidazol-4-ylmethyl)-10-methyl-6,9,12,15,18,21,24,27,30-nonaoxo-16-propan-2-yl-1,2-dithia-5,8,11,14,17,20,23,26,29-nonazacyclodotriacontane-4-carbonyl]amino]-5-[[(2S)-1-[[(2S)-1-[[(2S)-3-carboxy-1-[[(2S)-1-[[(2S)-1-[[(1S)-1-carboxyethyl]amino]-4-methyl-1-oxopentan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-1-oxopropan-2-yl]amino]-1-oxopropan-2-yl]amino]-3-(1H-imidazol-4-yl)-1-oxopropan-2-yl]amino]-5-oxopentanoic acid Chemical compound CC(C)C[C@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](C)NC(=O)[C@H](Cc1c[nH]cn1)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@@H]1CSSC[C@H](NC(=O)[C@@H](NC(=O)[C@@H]2CSSC[C@@H]3NC(=O)[C@H](Cc4ccccc4)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](NC(=O)[C@H](Cc4c[nH]cn4)NC(=O)[C@H](CO)NC(=O)[C@H](CC(O)=O)NC(=O)[C@@H]4CCCN4C(=O)[C@H](CSSC[C@H](NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](Cc4c[nH]cn4)NC(=O)[C@H](Cc4ccccc4)NC3=O)[C@@H](C)O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](Cc3ccccc3)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCCCN)C(=O)N3CCC[C@H]3C(=O)N[C@@H](C)C(=O)N2)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](Cc2ccccc2)NC(=O)[C@H](Cc2c[nH]cn2)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@@H](N)C(C)C)C(C)C)[C@@H](C)O)C(C)C)C(=O)N[C@@H](Cc2c[nH]cn2)C(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H](Cc2ccc(O)cc2)C(=O)N[C@@H](C(C)C)C(=O)NCC(=O)N[C@@H](C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N1)C(=O)N[C@@H](C)C(O)=O NMWKYTGJWUAZPZ-WWHBDHEGSA-N 0.000 description 1
- ZENKESXKWBIZCV-UHFFFAOYSA-N 2,2,4,4-tetrafluoro-1,3-benzodioxin-6-amine Chemical group O1C(F)(F)OC(F)(F)C2=CC(N)=CC=C21 ZENKESXKWBIZCV-UHFFFAOYSA-N 0.000 description 1
- QKNYBSVHEMOAJP-UHFFFAOYSA-N 2-amino-2-(hydroxymethyl)propane-1,3-diol;hydron;chloride Chemical compound Cl.OCC(N)(CO)CO QKNYBSVHEMOAJP-UHFFFAOYSA-N 0.000 description 1
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 1
- 241000590035 Achromobacter lyticus Species 0.000 description 1
- 229920001817 Agar Polymers 0.000 description 1
- 239000004475 Arginine Substances 0.000 description 1
- DCXYFEDJOCDNAF-UHFFFAOYSA-N Asparagine Natural products OC(=O)C(N)CC(N)=O DCXYFEDJOCDNAF-UHFFFAOYSA-N 0.000 description 1
- 102100026189 Beta-galactosidase Human genes 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- 241000282472 Canis lupus familiaris Species 0.000 description 1
- 241000283707 Capra Species 0.000 description 1
- 241000700198 Cavia Species 0.000 description 1
- 241000699800 Cricetinae Species 0.000 description 1
- 108010014303 DNA-directed DNA polymerase Proteins 0.000 description 1
- 102000016928 DNA-directed DNA polymerase Human genes 0.000 description 1
- 208000002699 Digestive System Neoplasms Diseases 0.000 description 1
- 239000004129 EU approved improving agent Substances 0.000 description 1
- 101800003838 Epidermal growth factor Proteins 0.000 description 1
- 241000283086 Equidae Species 0.000 description 1
- 241001337814 Erysiphe glycines Species 0.000 description 1
- 241000588724 Escherichia coli Species 0.000 description 1
- 241000620209 Escherichia coli DH5[alpha] Species 0.000 description 1
- 241000282326 Felis catus Species 0.000 description 1
- 241000699694 Gerbillinae Species 0.000 description 1
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 1
- 229920002527 Glycogen Polymers 0.000 description 1
- 102000005744 Glycoside Hydrolases Human genes 0.000 description 1
- 108010031186 Glycoside Hydrolases Proteins 0.000 description 1
- 102100029100 Hematopoietic prostaglandin D synthase Human genes 0.000 description 1
- 101100118545 Holotrichia diomphalia EGF-like gene Proteins 0.000 description 1
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 1
- ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 description 1
- AGPKZVBTJJNPAG-WHFBIAKZSA-N L-isoleucine Chemical compound CC[C@H](C)[C@H](N)C(O)=O AGPKZVBTJJNPAG-WHFBIAKZSA-N 0.000 description 1
- ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 description 1
- FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 description 1
- COLNVLDHVKWLRT-QMMMGPOBSA-N L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 description 1
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 1
- ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 description 1
- 108090001030 Lipoproteins Proteins 0.000 description 1
- 102000004895 Lipoproteins Human genes 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- 102100025751 Mothers against decapentaplegic homolog 2 Human genes 0.000 description 1
- 101710143123 Mothers against decapentaplegic homolog 2 Proteins 0.000 description 1
- 230000004988 N-glycosylation Effects 0.000 description 1
- CHJJGSNFBQVOTG-UHFFFAOYSA-N N-methyl-guanidine Natural products CNC(N)=N CHJJGSNFBQVOTG-UHFFFAOYSA-N 0.000 description 1
- 229920002274 Nalgene Polymers 0.000 description 1
- 102400000058 Neuregulin-1 Human genes 0.000 description 1
- 108090000556 Neuregulin-1 Proteins 0.000 description 1
- 239000000020 Nitrocellulose Substances 0.000 description 1
- 230000004989 O-glycosylation Effects 0.000 description 1
- 108020005187 Oligonucleotide Probes Proteins 0.000 description 1
- 108700020796 Oncogene Proteins 0.000 description 1
- 206010061902 Pancreatic neoplasm Diseases 0.000 description 1
- 241000237988 Patellidae Species 0.000 description 1
- 241001494479 Pecora Species 0.000 description 1
- 108010002747 Pfu DNA polymerase Proteins 0.000 description 1
- 102000004160 Phosphoric Monoester Hydrolases Human genes 0.000 description 1
- 108090000608 Phosphoric Monoester Hydrolases Proteins 0.000 description 1
- 241000288906 Primates Species 0.000 description 1
- 101710149951 Protein Tat Proteins 0.000 description 1
- 241000700159 Rattus Species 0.000 description 1
- 108020004511 Recombinant DNA Proteins 0.000 description 1
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 1
- 208000037065 Subacute sclerosing leukoencephalitis Diseases 0.000 description 1
- 206010042297 Subacute sclerosing panencephalitis Diseases 0.000 description 1
- 241000282887 Suidae Species 0.000 description 1
- 101710185710 Teratocarcinoma-derived growth factor 1 Proteins 0.000 description 1
- 102400001320 Transforming growth factor alpha Human genes 0.000 description 1
- 101800004564 Transforming growth factor alpha Proteins 0.000 description 1
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 1
- 239000007983 Tris buffer Substances 0.000 description 1
- 241000269370 Xenopus <genus> Species 0.000 description 1
- 238000002835 absorbance Methods 0.000 description 1
- 238000011481 absorbance measurement Methods 0.000 description 1
- 238000010306 acid treatment Methods 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 239000008272 agar Substances 0.000 description 1
- 239000011543 agarose gel Substances 0.000 description 1
- 125000003295 alanine group Chemical group N[C@@H](C)C(=O)* 0.000 description 1
- 108091005588 alkylated proteins Proteins 0.000 description 1
- 230000029936 alkylation Effects 0.000 description 1
- 238000005804 alkylation reaction Methods 0.000 description 1
- 102000012086 alpha-L-Fucosidase Human genes 0.000 description 1
- 108010061314 alpha-L-Fucosidase Proteins 0.000 description 1
- AFVLVVWMAFSXCK-VMPITWQZSA-N alpha-cyano-4-hydroxycinnamic acid Chemical compound OC(=O)C(\C#N)=C\C1=CC=C(O)C=C1 AFVLVVWMAFSXCK-VMPITWQZSA-N 0.000 description 1
- 230000004075 alteration Effects 0.000 description 1
- 150000003862 amino acid derivatives Chemical class 0.000 description 1
- AVKUERGKIZMTKX-NJBDSQKTSA-N ampicillin Chemical compound C1([C@@H](N)C(=O)N[C@H]2[C@H]3SC([C@@H](N3C2=O)C(O)=O)(C)C)=CC=CC=C1 AVKUERGKIZMTKX-NJBDSQKTSA-N 0.000 description 1
- 229960000723 ampicillin Drugs 0.000 description 1
- 210000004102 animal cell Anatomy 0.000 description 1
- 230000003217 anti-cancerogenic effect Effects 0.000 description 1
- 230000000259 anti-tumor effect Effects 0.000 description 1
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 1
- 235000009582 asparagine Nutrition 0.000 description 1
- 229960001230 asparagine Drugs 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- 230000001580 bacterial effect Effects 0.000 description 1
- 108010005774 beta-Galactosidase Proteins 0.000 description 1
- 230000008827 biological function Effects 0.000 description 1
- 210000000988 bone and bone Anatomy 0.000 description 1
- 210000004556 brain Anatomy 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 239000006172 buffering agent Substances 0.000 description 1
- 244000309466 calf Species 0.000 description 1
- -1 cationic lipid Chemical class 0.000 description 1
- 238000004113 cell culture Methods 0.000 description 1
- 230000012292 cell migration Effects 0.000 description 1
- 230000010307 cell transformation Effects 0.000 description 1
- 230000036755 cellular response Effects 0.000 description 1
- 210000000038 chest Anatomy 0.000 description 1
- 235000012000 cholesterol Nutrition 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 239000000512 collagen gel Substances 0.000 description 1
- 208000029742 colonic neoplasm Diseases 0.000 description 1
- 230000002860 competitive effect Effects 0.000 description 1
- 238000010276 construction Methods 0.000 description 1
- 235000018417 cysteine Nutrition 0.000 description 1
- 230000006866 deterioration Effects 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 238000003745 diagnosis Methods 0.000 description 1
- 230000001079 digestive effect Effects 0.000 description 1
- SWSQBOPZIKWTGO-UHFFFAOYSA-N dimethylaminoamidine Natural products CN(C)C(N)=N SWSQBOPZIKWTGO-UHFFFAOYSA-N 0.000 description 1
- 208000037765 diseases and disorders Diseases 0.000 description 1
- 208000035475 disorder Diseases 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 239000003792 electrolyte Substances 0.000 description 1
- 210000002257 embryonic structure Anatomy 0.000 description 1
- 230000002255 enzymatic effect Effects 0.000 description 1
- 229940116977 epidermal growth factor Drugs 0.000 description 1
- 235000019253 formic acid Nutrition 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 108020001507 fusion proteins Proteins 0.000 description 1
- 102000037865 fusion proteins Human genes 0.000 description 1
- 230000005021 gait Effects 0.000 description 1
- 230000002496 gastric effect Effects 0.000 description 1
- 235000013922 glutamic acid Nutrition 0.000 description 1
- 239000004220 glutamic acid Substances 0.000 description 1
- ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 1
- 229940096919 glycogen Drugs 0.000 description 1
- 230000013595 glycosylation Effects 0.000 description 1
- 238000006206 glycosylation reaction Methods 0.000 description 1
- 239000011544 gradient gel Substances 0.000 description 1
- 210000003128 head Anatomy 0.000 description 1
- 108060003552 hemocyanin Proteins 0.000 description 1
- 230000013632 homeostatic process Effects 0.000 description 1
- 230000002209 hydrophobic effect Effects 0.000 description 1
- 238000003384 imaging method Methods 0.000 description 1
- 150000003949 imides Chemical class 0.000 description 1
- 210000001822 immobilized cell Anatomy 0.000 description 1
- 230000000984 immunochemical effect Effects 0.000 description 1
- 229940072221 immunoglobulins Drugs 0.000 description 1
- 239000007943 implant Substances 0.000 description 1
- 238000002513 implantation Methods 0.000 description 1
- 238000000099 in vitro assay Methods 0.000 description 1
- 230000006698 induction Effects 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 238000009434 installation Methods 0.000 description 1
- 230000000968 intestinal effect Effects 0.000 description 1
- 238000001361 intraarterial administration Methods 0.000 description 1
- 238000007917 intracranial administration Methods 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000007912 intraperitoneal administration Methods 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 238000007914 intraventricular administration Methods 0.000 description 1
- PGLTVOMIXTUURA-UHFFFAOYSA-N iodoacetamide Chemical compound NC(=O)CI PGLTVOMIXTUURA-UHFFFAOYSA-N 0.000 description 1
- 229960000310 isoleucine Drugs 0.000 description 1
- AGPKZVBTJJNPAG-UHFFFAOYSA-N isoleucine Natural products CCC(C)C(N)C(O)=O AGPKZVBTJJNPAG-UHFFFAOYSA-N 0.000 description 1
- 238000009533 lab test Methods 0.000 description 1
- 239000003446 ligand Substances 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 230000004807 localization Effects 0.000 description 1
- 238000003468 luciferase reporter gene assay Methods 0.000 description 1
- 210000004072 lung Anatomy 0.000 description 1
- 229910001629 magnesium chloride Inorganic materials 0.000 description 1
- 238000002595 magnetic resonance imaging Methods 0.000 description 1
- 208000015486 malignant pancreatic neoplasm Diseases 0.000 description 1
- 210000001161 mammalian embryo Anatomy 0.000 description 1
- 210000005075 mammary gland Anatomy 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 238000013507 mapping Methods 0.000 description 1
- 238000001819 mass spectrum Methods 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 229930182817 methionine Natural products 0.000 description 1
- 238000013508 migration Methods 0.000 description 1
- 230000005012 migration Effects 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 238000012544 monitoring process Methods 0.000 description 1
- 230000009826 neoplastic cell growth Effects 0.000 description 1
- 229940060155 neuac Drugs 0.000 description 1
- 229920001220 nitrocellulos Polymers 0.000 description 1
- 238000007899 nucleic acid hybridization Methods 0.000 description 1
- 239000002751 oligonucleotide probe Substances 0.000 description 1
- 238000002515 oligonucleotide synthesis Methods 0.000 description 1
- 150000002482 oligosaccharides Polymers 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 230000002018 overexpression Effects 0.000 description 1
- 201000002528 pancreatic cancer Diseases 0.000 description 1
- 208000008443 pancreatic carcinoma Diseases 0.000 description 1
- 239000008188 pellet Substances 0.000 description 1
- COLNVLDHVKWLRT-UHFFFAOYSA-N phenylalanine Natural products OC(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-N 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 238000003752 polymerase chain reaction Methods 0.000 description 1
- 229920001282 polysaccharide Polymers 0.000 description 1
- 239000005017 polysaccharide Substances 0.000 description 1
- 230000004481 post-translational protein modification Effects 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- 210000002307 prostate Anatomy 0.000 description 1
- 230000009145 protein modification Effects 0.000 description 1
- 230000002797 proteolythic effect Effects 0.000 description 1
- 239000011535 reaction buffer Substances 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 238000012216 screening Methods 0.000 description 1
- 239000004017 serum-free culture medium Substances 0.000 description 1
- 230000007781 signaling event Effects 0.000 description 1
- 230000037432 silent mutation Effects 0.000 description 1
- 238000002741 site-directed mutagenesis Methods 0.000 description 1
- 239000001632 sodium acetate Substances 0.000 description 1
- 235000017281 sodium acetate Nutrition 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 238000004114 suspension culture Methods 0.000 description 1
- 238000013268 sustained release Methods 0.000 description 1
- 239000012730 sustained-release form Substances 0.000 description 1
- 238000007910 systemic administration Methods 0.000 description 1
- 238000010998 test method Methods 0.000 description 1
- 238000011200 topical administration Methods 0.000 description 1
- 238000013518 transcription Methods 0.000 description 1
- 230000035897 transcription Effects 0.000 description 1
- 230000005030 transcription termination Effects 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- 230000009261 transgenic effect Effects 0.000 description 1
- 238000013519 translation Methods 0.000 description 1
- 230000001960 triggered effect Effects 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
- 230000004614 tumor growth Effects 0.000 description 1
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 1
- 239000002691 unilamellar liposome Substances 0.000 description 1
- VBEQCZHXXJYVRD-GACYYNSASA-N uroanthelone Chemical compound C([C@@H](C(=O)N[C@H](C(=O)N[C@@H](CS)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CS)C(=O)N[C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)NCC(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CS)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O)C(C)C)[C@@H](C)O)NC(=O)[C@H](CO)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CO)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@@H](NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@H](CCSC)NC(=O)[C@H](CS)NC(=O)[C@@H](NC(=O)CNC(=O)CNC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CS)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)CNC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CS)NC(=O)CNC(=O)[C@H]1N(CCC1)C(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@@H](N)CC(N)=O)C(C)C)[C@@H](C)CC)C1=CC=C(O)C=C1 VBEQCZHXXJYVRD-GACYYNSASA-N 0.000 description 1
- 230000003612 virological effect Effects 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
- 239000003643 water by type Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/475—Growth factors; Growth regulators
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A61P35/02—Antineoplastic agents specific for leukemia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Genetics & Genomics (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Pharmacology & Pharmacy (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Animal Behavior & Ethology (AREA)
- Molecular Biology (AREA)
- Public Health (AREA)
- Toxicology (AREA)
- Veterinary Medicine (AREA)
- Biochemistry (AREA)
- Gastroenterology & Hepatology (AREA)
- Zoology (AREA)
- Biophysics (AREA)
- General Chemical & Material Sciences (AREA)
- Hematology (AREA)
- Oncology (AREA)
- Peptides Or Proteins (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US23314800P | 2000-09-18 | 2000-09-18 | |
| PCT/US2001/029066 WO2002022808A2 (en) | 2000-09-18 | 2001-09-18 | Cripto mutant and uses thereof |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| NZ525380A true NZ525380A (en) | 2008-06-30 |
Family
ID=22876077
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NZ525380A NZ525380A (en) | 2000-09-18 | 2001-09-18 | Non-fucosylated forms of Cripto and their use as tumor blocking agents |
Country Status (7)
| Country | Link |
|---|---|
| US (1) | US7604931B2 (https=) |
| EP (1) | EP1320604A2 (https=) |
| JP (1) | JP2004524810A (https=) |
| AU (2) | AU9272401A (https=) |
| CA (1) | CA2422814A1 (https=) |
| NZ (1) | NZ525380A (https=) |
| WO (1) | WO2002022808A2 (https=) |
Families Citing this family (86)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AUPR395801A0 (en) | 2001-03-26 | 2001-04-26 | Austin Research Institute, The | Antibodies against cancer |
| US20090123470A1 (en) * | 2001-03-26 | 2009-05-14 | The Macfarlane Burnet Istitute For Medical Research And Public Health Ltd. | Antibodies Against Cancer |
| US7582299B2 (en) | 2001-04-26 | 2009-09-01 | Biogen Idec Ma Inc. | Cripto-specific antibodies |
| PL207087B1 (pl) | 2001-04-26 | 2010-10-29 | Biogen | Przeciwciało, które wiąże się swoiście z białkiem Cripto, zawierająca je kompozycja farmaceutyczna i zastosowanie przeciwciała |
| DK1670511T3 (da) | 2003-09-15 | 2009-11-23 | Res Dev Foundation | Cripto-antagonisme af activin- og TGF-B-signalering |
| CA2539535A1 (en) * | 2003-10-03 | 2005-04-14 | Government Of The United States Of America, Represented By The Secretary , Department Of Health And Human Services | Use of cripto-1 as a biomarker for neurodegenerative disease and method of inhibiting progression thereof |
| EP2478912B1 (en) | 2003-11-06 | 2016-08-31 | Seattle Genetics, Inc. | Auristatin conjugates with anti-HER2 or anti-CD22 antibodies and their use in therapy |
| NZ579482A (en) | 2004-06-01 | 2011-02-25 | Genentech Inc | Antibody drug conjugates and methods |
| US20100111856A1 (en) | 2004-09-23 | 2010-05-06 | Herman Gill | Zirconium-radiolabeled, cysteine engineered antibody conjugates |
| DK1791565T3 (en) | 2004-09-23 | 2016-08-01 | Genentech Inc | Cysteingensplejsede antibodies and conjugates |
| EP1838736B1 (en) | 2005-01-05 | 2013-03-06 | Biogen Idec MA Inc. | Cripto binding molecules |
| EP1846443A4 (en) * | 2005-01-07 | 2008-07-23 | Glaxo Group Ltd | NEW USE |
| US20100041032A1 (en) * | 2006-04-28 | 2010-02-18 | Biogen Idec Ma Inc. | Composition and methods for the detection of cripto-3 |
| DE602007008872D1 (de) * | 2006-05-02 | 2010-10-14 | Genentech Inc | Mikrowellengestützte deglycosylierung von proteinen zur molekulargewichtsbestimmung durch massenspektrometrie |
| WO2008040759A1 (en) * | 2006-10-03 | 2008-04-10 | Pharmexa A/S | Method for down-regulation of cripto |
| JP2013504585A (ja) | 2009-09-09 | 2013-02-07 | セントローズ， エルエルシー | 細胞外標的化薬物複合体 |
| SI2528625T1 (sl) | 2010-04-15 | 2013-11-29 | Spirogen Sarl | Pirolobenzodiazepini in njihovi konjugati |
| CA2799540A1 (en) | 2010-06-08 | 2011-12-15 | Genentech, Inc. | Cysteine engineered antibodies and conjugates |
| US20120121615A1 (en) | 2010-11-17 | 2012-05-17 | Flygare John A | Alaninyl maytansinol antibody conjugates |
| US8679767B2 (en) | 2011-05-12 | 2014-03-25 | Genentech, Inc. | Multiple reaction monitoring LC-MS/MS method to detect therapeutic antibodies in animal samples using framework signature peptides |
| BR112014009050B1 (pt) | 2011-10-14 | 2022-06-21 | Medimmune Limited | Conjugado anticorpo-fármaco de pirrolbenzodiazepinas, composição farmacêutica que compreende o mesmo, bem como compostos de pirrolbenzodiazepinas |
| WO2013130093A1 (en) | 2012-03-02 | 2013-09-06 | Genentech, Inc. | Biomarkers for treatment with anti-tubulin chemotherapeutic compounds |
| RS57694B1 (sr) | 2012-10-12 | 2018-11-30 | Adc Therapeutics Sa | Pirolobenzodiazepin - anti-psma konjugati antitela |
| JP6392765B2 (ja) | 2012-10-12 | 2018-09-19 | エイディーシー・セラピューティクス・エス・アーＡｄｃ Ｔｈｅｒａｐｅｕｔｉｃｓ Ｓａ | ピロロベンゾジアゼピン−抗体結合体 |
| MX338711B (es) | 2012-10-12 | 2016-04-28 | Medimmune Ltd | Pirrolobenzodiazepinas y conjugados de las mismas. |
| HRP20182129T1 (hr) | 2012-10-12 | 2019-02-08 | Adc Therapeutics Sa | Konjugati protutijelo - pirolobenzodiazepin |
| EP2906296B1 (en) | 2012-10-12 | 2018-03-21 | ADC Therapeutics SA | Pyrrolobenzodiazepine-antibody conjugates |
| ES2680153T3 (es) | 2012-10-12 | 2018-09-04 | Adc Therapeutics Sa | Conjugados de anticuerpos anti-PSMA-pirrolobenzodiazepinas |
| EP2906297B1 (en) | 2012-10-12 | 2017-12-06 | ADC Therapeutics SA | Pyrrolobenzodiazepine-antibody conjugates |
| CN110627797A (zh) | 2012-12-21 | 2019-12-31 | 麦迪穆有限责任公司 | 用于治疗增殖性和自身免疫疾病的非对称吡咯并苯并二氮杂卓二聚物 |
| CN105189507A (zh) | 2012-12-21 | 2015-12-23 | 斯皮罗根有限公司 | 吡咯并苯并二氮杂卓及其结合物 |
| MX362970B (es) | 2013-03-13 | 2019-02-28 | Medimmune Ltd | Pirrolobenzodiazepinas y conjugados de las mismas. |
| TWI680766B (zh) | 2013-03-13 | 2020-01-01 | 英商梅迪繆思有限公司 | 吡咯并苯并二氮呯及其共軛物 |
| AU2014229529B2 (en) | 2013-03-13 | 2018-02-15 | Medimmune Limited | Pyrrolobenzodiazepines and conjugates thereof |
| BR112016002829A2 (pt) | 2013-08-12 | 2017-09-19 | Genentech Inc | Composto e processo para preparar o composto de conjugado anticorpo-¿droga, composição farmacêutica, método de tratamento do câncer, kit para o tratamento do câncer, intermediário ligante¿-droga, porção e composto de porção droga de dímero cbi |
| GB201317982D0 (en) | 2013-10-11 | 2013-11-27 | Spirogen Sarl | Pyrrolobenzodiazepines and conjugates thereof |
| EP3054983B1 (en) | 2013-10-11 | 2019-03-20 | Medimmune Limited | Pyrrolobenzodiazepine-antibody conjugates |
| WO2015052534A1 (en) | 2013-10-11 | 2015-04-16 | Spirogen Sàrl | Pyrrolobenzodiazepine-antibody conjugates |
| WO2015052535A1 (en) | 2013-10-11 | 2015-04-16 | Spirogen Sàrl | Pyrrolobenzodiazepine-antibody conjugates |
| WO2015095227A2 (en) | 2013-12-16 | 2015-06-25 | Genentech, Inc. | Peptidomimetic compounds and antibody-drug conjugates thereof |
| EP3082876B1 (en) | 2013-12-16 | 2018-01-17 | Genentech, Inc. | 1-(chloromethyl)-2,3-dihydro-1h-benzo[e]indole dimer antibody-drug conjugate compounds, and methods of use and treatment |
| JP6671292B2 (ja) | 2013-12-16 | 2020-03-25 | ジェネンテック， インコーポレイテッド | ペプチド模倣化合物及びその抗体−薬物コンジュゲート |
| EP3193940A1 (en) | 2014-09-10 | 2017-07-26 | Medimmune Limited | Pyrrolobenzodiazepines and conjugates thereof |
| SG11201701128YA (en) | 2014-09-12 | 2017-03-30 | Genentech Inc | Cysteine engineered antibodies and conjugates |
| GB201416112D0 (en) | 2014-09-12 | 2014-10-29 | Medimmune Ltd | Pyrrolobenzodiazepines and conjugates thereof |
| WO2016040825A1 (en) | 2014-09-12 | 2016-03-17 | Genentech, Inc. | Anthracycline disulfide intermediates, antibody-drug conjugates and methods |
| CN107073136A (zh) | 2014-09-17 | 2017-08-18 | 健泰科生物技术公司 | 吡咯并苯并二氮杂卓及其抗体二硫化物偶联物 |
| CN107148285B (zh) | 2014-11-25 | 2022-01-04 | Adc治疗股份有限公司 | 吡咯并苯并二氮杂䓬-抗体缀合物 |
| AU2015358532C1 (en) | 2014-12-03 | 2020-10-29 | Genentech, Inc. | Quaternary amine compounds and antibody-drug conjugates thereof |
| GB201506411D0 (en) | 2015-04-15 | 2015-05-27 | Bergenbio As | Humanized anti-axl antibodies |
| GB201506402D0 (en) | 2015-04-15 | 2015-05-27 | Berkel Patricius H C Van And Howard Philip W | Site-specific antibody-drug conjugates |
| CR20180243A (es) | 2015-10-02 | 2018-07-31 | Genentech Inc | Conjugados de anticuerpo-fármaco de pirrolobenzodiazepina y métodos de uso |
| MA43354A (fr) | 2015-10-16 | 2018-08-22 | Genentech Inc | Conjugués médicamenteux à pont disulfure encombré |
| EP3365025B1 (en) | 2015-10-20 | 2020-07-15 | Genentech, Inc. | Calicheamicin-antibody-drug conjugates and methods of use |
| GB201601431D0 (en) | 2016-01-26 | 2016-03-09 | Medimmune Ltd | Pyrrolobenzodiazepines |
| GB201602356D0 (en) | 2016-02-10 | 2016-03-23 | Medimmune Ltd | Pyrrolobenzodiazepine Conjugates |
| GB201602359D0 (en) | 2016-02-10 | 2016-03-23 | Medimmune Ltd | Pyrrolobenzodiazepine Conjugates |
| CN108700598A (zh) | 2016-03-25 | 2018-10-23 | 豪夫迈·罗氏有限公司 | 多路总抗体和抗体缀合的药物量化测定法 |
| GB201607478D0 (en) | 2016-04-29 | 2016-06-15 | Medimmune Ltd | Pyrrolobenzodiazepine Conjugates |
| CN118436801A (zh) | 2016-05-20 | 2024-08-06 | 豪夫迈·罗氏有限公司 | Protac抗体缀合物及其使用方法 |
| EP3465221B1 (en) | 2016-05-27 | 2020-07-22 | H. Hoffnabb-La Roche Ag | Bioanalytical method for the characterization of site-specific antibody-drug conjugates |
| WO2017214024A1 (en) | 2016-06-06 | 2017-12-14 | Genentech, Inc. | Silvestrol antibody-drug conjugates and methods of use |
| CN109689111B (zh) | 2016-08-11 | 2024-04-05 | 基因泰克公司 | 吡咯并苯并二氮杂䓬前药及其抗体缀合物 |
| JP7050770B2 (ja) | 2016-10-05 | 2022-04-08 | エフ・ホフマン－ラ・ロシュ・アクチェンゲゼルシャフト | 抗体薬物コンジュゲートの調製方法 |
| GB201617466D0 (en) | 2016-10-14 | 2016-11-30 | Medimmune Ltd | Pyrrolobenzodiazepine conjugates |
| GB201702031D0 (en) | 2017-02-08 | 2017-03-22 | Medlmmune Ltd | Pyrrolobenzodiazepine-antibody conjugates |
| RS61795B1 (sr) | 2017-02-08 | 2021-06-30 | Adc Therapeutics Sa | Konjugati pirolobenzodiazepin antitela |
| CN110582505B (zh) | 2017-04-18 | 2021-04-02 | 免疫医疗有限公司 | 吡咯并苯并二氮杂*缀合物 |
| WO2018193102A1 (en) | 2017-04-20 | 2018-10-25 | Adc Therapeutics Sa | Combination therapy with an anti-axl antibody-drug conjugate |
| CA3064804A1 (en) | 2017-06-14 | 2018-12-20 | Adc Therapeutics Sa | Dosage regimes for the administration of an anti-cd19 adc |
| KR102270107B1 (ko) | 2017-08-18 | 2021-06-30 | 메디뮨 리미티드 | 피롤로벤조디아제핀 컨쥬게이트 |
| EP3684773B1 (en) | 2017-09-20 | 2026-04-29 | pH Pharma Co., Ltd. | Thailanstatin analogs |
| GB201803342D0 (en) | 2018-03-01 | 2018-04-18 | Medimmune Ltd | Methods |
| GB201806022D0 (en) | 2018-04-12 | 2018-05-30 | Medimmune Ltd | Pyrrolobenzodiazepines and conjugates thereof |
| GB201814281D0 (en) | 2018-09-03 | 2018-10-17 | Femtogenix Ltd | Cytotoxic agents |
| JP7708662B2 (ja) | 2018-10-24 | 2025-07-15 | エフ・ホフマン－ラ・ロシュ・アクチェンゲゼルシャフト | コンジュゲート化された化学的分解誘導物質および使用方法 |
| JP2022513198A (ja) | 2018-12-10 | 2022-02-07 | ジェネンテック， インコーポレイテッド | Ｆｃ含有タンパク質への部位特異的コンジュゲーションのための光架橋性ペプチド |
| GB201901197D0 (en) | 2019-01-29 | 2019-03-20 | Femtogenix Ltd | G-A Crosslinking cytotoxic agents |
| CN113631560B (zh) | 2019-03-15 | 2025-02-18 | 麦迪穆有限责任公司 | 氮杂环丁烷并苯并二氮杂䓬二聚体和用于治疗癌症的包含它们的缀合物 |
| GB2597532A (en) | 2020-07-28 | 2022-02-02 | Femtogenix Ltd | Cytotoxic compounds |
| EP4426727A2 (en) | 2021-11-03 | 2024-09-11 | Hangzhou Dac Biotech Co., Ltd. | Specific conjugation of an antibody |
| IT202200007580A1 (it) * | 2022-04-15 | 2023-10-15 | Consiglio Nazionale Ricerche | Vescicole lipidiche per l’uso nel trattamento terapeutico di tumori aggressivi |
| WO2024138128A2 (en) | 2022-12-23 | 2024-06-27 | Genentech, Inc. | Cereblon degrader conjugates, and uses thereof |
| KR20260012304A (ko) | 2023-04-17 | 2026-01-26 | 피크 바이오, 인크. | 항체 및 항체-약물 접합체 및 사용 방법 및 합성 공정 및 중간체 |
| WO2026006689A2 (en) | 2024-06-28 | 2026-01-02 | Firefly Bio, Inc. | Bcl-xl degrader antibody conjugates and uses thereof |
| WO2026006688A2 (en) | 2024-06-28 | 2026-01-02 | Firefly Bio, Inc. | Degrader antibody conjugates and uses thereof |
Family Cites Families (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5256643A (en) * | 1990-05-29 | 1993-10-26 | The Government Of The United States | Human cripto protein |
| US5264557A (en) * | 1991-08-23 | 1993-11-23 | The United States Of America As Represented By The Department Of Health And Human Services | Polypeptide of a human cripto-related gene, CR-3 |
| MX9707617A (es) * | 1995-06-05 | 1997-12-31 | Human Genome Sciences Inc | Factor de crecimiento de criptina humano. |
| DE69737457T2 (de) * | 1997-01-31 | 2007-11-29 | Genentech, Inc., South San Francisco | O-fukosyltransferase |
| WO1999045026A1 (en) * | 1998-03-05 | 1999-09-10 | Chiron Corporation | Method for increasing the serum half-life of a biologically active molecule |
| IL125608A0 (en) * | 1998-07-30 | 1999-03-12 | Yeda Res & Dev | Tumor associated antigen peptides and use of same as anti-tumor vaccines |
-
2001
- 2001-09-18 NZ NZ525380A patent/NZ525380A/en unknown
- 2001-09-18 CA CA002422814A patent/CA2422814A1/en not_active Abandoned
- 2001-09-18 WO PCT/US2001/029066 patent/WO2002022808A2/en not_active Ceased
- 2001-09-18 JP JP2002527250A patent/JP2004524810A/ja active Pending
- 2001-09-18 EP EP01973111A patent/EP1320604A2/en not_active Withdrawn
- 2001-09-18 AU AU9272401A patent/AU9272401A/xx active Pending
- 2001-09-18 AU AU2001292724A patent/AU2001292724B2/en not_active Ceased
-
2003
- 2003-03-17 US US10/390,566 patent/US7604931B2/en not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| AU2001292724B2 (en) | 2005-05-26 |
| US20030232755A1 (en) | 2003-12-18 |
| EP1320604A2 (en) | 2003-06-25 |
| AU9272401A (en) | 2002-03-26 |
| JP2004524810A (ja) | 2004-08-19 |
| US7604931B2 (en) | 2009-10-20 |
| CA2422814A1 (en) | 2002-03-21 |
| WO2002022808A3 (en) | 2003-01-16 |
| WO2002022808A2 (en) | 2002-03-21 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US7604931B2 (en) | Cripto mutant and uses thereof | |
| AU2001292724A1 (en) | CRIPTO mutant and uses thereof | |
| KR101220245B1 (ko) | 성장인자에 결합하는 융합 단백질 | |
| KR100611620B1 (ko) | 안지오포이에틴 수용체 결합 도메인 및 다중체화 도메인을포함하는 융합 단백질 | |
| AU728614B2 (en) | Cerebellum-derived growth factors, and uses related thereto | |
| EP1259544B1 (en) | Heterologous polypeptide of the tnf family | |
| JP2022048160A (ja) | Ｂｍｐ－ａｌｋ３アンタゴニストおよび骨成長促進のためのその使用 | |
| EP0599274A1 (en) | HER4, a human receptor tyrosine kinase of the epidermal growth factor receptor family | |
| JP2020158546A (ja) | 筋ジストロフィー治療のためのユートロフィン誘導に関するａｃｔｒｉｉｂタンパク質およびその改変体およびその使用 | |
| JP2007044044A (ja) | 線維芽細胞増殖因子様ポリペプチド | |
| WO1997009425A9 (en) | Cerebellum-derived growth factors, and uses related thereto | |
| SK152498A3 (en) | Nucleic acid coding c-ret ligand, polypeptid ligand c-ret, process for the preparation thereof and use for stimulating neural and renal growth | |
| AU735794B2 (en) | Don-1 gene and polypeptides and uses therefor | |
| AU2714700A (en) | Method of enhancing the biological activity of ligands | |
| AU2001266876B2 (en) | Pleiotrophin growth factor receptor for the treatment of proliferative, vascular and neurological disorders | |
| WO2001016169A2 (en) | RET LIGAND 5 (Retl5) FROM HUMAN AND MOUSE | |
| CN102134275B (zh) | 表皮生长因子受体变异体 | |
| AU2005204268B2 (en) | CRIPTO Mutant and Uses Thereof | |
| CN102443056B (zh) | 表皮生长因子受体的外显子缺失变异体 | |
| AU2007200329A1 (en) | CRIPTO Mutant and Uses Thereof | |
| Wu | Tumorigenesis of A431 human epidermoid carcinoma cell |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PSEA | Patent sealed | ||
| RENW | Renewal (renewal fees accepted) |